title: Roles of chemokine receptor 4 (CXCR4) and chemokine ligand 12 (CXCL12) in metastasis of hepatocellular carcinoma cells.
abstract: Chemokines are involved in human hepatocellular carcinoma (HCC) carcinogenesis. However, the exact mechanism of chemokines in HCC carcinogenesis remains unknown. Here we investigated the roles of chemokine receptor 4 (CXCR4) and chemokine ligand 12 (CXCL12) in the metastasis of HCC. We found that the expression levels of CXCR4 mRNA in HCC tissues, MHCC97 cells, and HUVEC cells were 2.52 +/- 1.13, 2.34 +/- 1.16 and 1.63 +/- 1.26, respectively and that the CXCR4 protein levels were 1.38 +/- 0.13, 1.96 +/- 0.32 and 1.86 +/- 0.21, respectively. In contrast, CXCR4 was not detected in normal hepatic tissues. In 78 HCC patients, we also found that the concentration of CXCL12 in cancerous ascitic fluid was 783-8,364 pg/ml and that CXCL12 mRNA level in HCC metastasis portal lymph nodes was 1.21 +/- 0.87 but undetectable in normal hepatic tissues. Finally we discovered that recombinant human CXCL12 could induce MHCC97 cells and HUVEC cells to migrate with chemotactic indexes (CI) of 3.9 +/- 1.1 and 4.1 +/- 1.6, respectively. Cancerous ascitic fluid could also induce the migration of MHCC97 cells with a CI of 1.9 +/- 0.8. Thus, our data suggest that CXCR4 and CXCL12 may play an important role in the metastasis of HCC by promoting the migration of tumor cells.
authors.affiliation: The 3rd Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Zeya
authors.initials: Z
authors.lastname: Pan
authors.forename: Aijun
authors.initials: A
authors.lastname: Li
authors.forename: Siyuan
authors.initials: S
authors.lastname: Fu
authors.forename: Yin
authors.initials: Y
authors.lastname: Lei
authors.forename: Hangyong
authors.initials: H
authors.lastname: Sun
authors.forename: Mengchao
authors.initials: M
authors.lastname: Wu
authors.forename: Weiping
authors.initials: W
authors.lastname: Zhou
mesh_terms: D001202:Ascitic Fluid / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000556:secondary; D002465:Cell Movement; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000502:physiology*; D002633:Chemotaxis; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D019718:Receptors, CXCR4 / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D011994:Recombinant Proteins